OPHTHALMIC ARACHIDONYLETHANOLAMIDE DECREASES INTRAOCULAR-PRESSURE IN NORMOTENSIVE RABBITS

Arachidonylethanolamide (AEA) was the first anandamide to be identifie d as an endogenous ligand for the cannabinoid receptor of porcine brai n. Since cannabinoids have shown some value in the reduction of ocular hypertension, the title compound was evaluated in normotensive rabbit s as a possible topically applied agent for reducing intraocular press ure. AEA was dissolved in an aqueous solution of 2-hydroxypropyl-beta- cyclodextrin. Single eyedrops (25 mu l) containing 3.13, 6.25, 31.25, 62.5 or 125.0 mu g of AEA were instilled unilaterally into eyes of nor motensive albino and pigmented rabbits. The intraocular pressures (IOP s) of these rabbits were then measured at fixed time intervals. The ef fect of AEA on IOP in treated and untreated (contralateral) eyes was s imilar in both types of rabbits. Administration of 31.25 mu g of AEA c aused an immediate IOP reduction in the treated eyes. AEA doses of 62. 5 mu g caused an initial increase and subsequent decrease of IOP in th e treated eyes. In the untreated eyes, a marginal ocular hypotensive r esponse of limited duration occurred immediately after administration of AEA at doses 31.25 or 62.5 mu g. A significant increase (without su bsequent decrease below baseline) in IOP occurred in treated eyes afte r a dose of 125.0 mu g. The lowest dose (3.13 mu g) did not have an ef fect on IOP. This study constitutes the first published demonstration that topical, unilateral administration of AEA significantly decreases IOP in normotensive albino and pigmented rabbits. Although the mechan ism of action by which this compound produces its hypotensive effect i n the eye is not known, the results suggest that AEA may prove useful in the investigation of glaucoma therapy.